Prediction of UGT-mediated Metabolism Using the Manually Curated MetaQSAR Database.

Details

Serval ID
serval:BIB_4C8B117A4D15
Type
Article: article from journal or magazin.
Publication sub-type
Letter (letter): Communication to the publisher.
Collection
Publications
Institution
Title
Prediction of UGT-mediated Metabolism Using the Manually Curated MetaQSAR Database.
Journal
ACS medicinal chemistry letters
Author(s)
Mazzolari A., Afzal A.M., Pedretti A., Testa B., Vistoli G., Bender A.
ISSN
1948-5875 (Print)
ISSN-L
1948-5875
Publication state
Published
Issued date
11/04/2019
Peer-reviewed
Oui
Volume
10
Number
4
Pages
633-638
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Even though glucuronidations are the most frequent metabolic reactions of conjugation, both in quantitative and qualitative terms, they have rather seldom been investigated using computational approaches. To fill this gap, we have used the manually collected MetaQSAR metabolic reaction database to generate two models for the prediction of UGT-mediated metabolism, both based on molecular descriptors and implementing the Random Forest algorithm. The first model predicts the occurrence of the reaction and was internally validated with a Matthew correlation coefficient (MCC) of 0.76 and an area under the ROC curve (AUC) of 0.94, and further externally validated using a test set composed of 120 additional xenobiotics (MCC of 0.70 and AUC of 0.90). The second model distinguishes between O- and N-glucuronidations and was optimized by the random undersampling procedure to improve the predictive accuracy during the internal validation, with the recall measure of the minority class increasing from 0.55 to 0.78.
Pubmed
Web of science
Create date
05/05/2019 14:52
Last modification date
20/08/2019 14:01
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